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Articles 1 - 8 of 8
Full-Text Articles in Pathology
Dystrophic Microglia Are Associated With Neurodegenerative Disease And Not Healthy Aging In The Human Brain, Ryan K. Shahidehpour, Rebecca E. Higdon, Nicole G. Crawford, Janna H. Neltner, Eseosa T. Ighodaro, Ela Patel, Douglas Price, Peter T. Nelson, Adam D. Bachstetter
Dystrophic Microglia Are Associated With Neurodegenerative Disease And Not Healthy Aging In The Human Brain, Ryan K. Shahidehpour, Rebecca E. Higdon, Nicole G. Crawford, Janna H. Neltner, Eseosa T. Ighodaro, Ela Patel, Douglas Price, Peter T. Nelson, Adam D. Bachstetter
Spinal Cord and Brain Injury Research Center Faculty Publications
Loss of physiological microglial function may increase the propagation of neurodegenerative diseases. Cellular senescence is a hallmark of aging; thus, we hypothesized age could be a cause of dystrophic microglia. Stereological counts were performed for total microglia, 2 microglia morphologies (hypertrophic and dystrophic) across the human lifespan. An age-associated increase in the number of dystrophic microglia was found in the hippocampus and frontal cortex. However, the increase in dystrophic microglia was proportional to the age-related increase in the total number of microglia. Thus, aging alone does not explain the presence of dystrophic microglia. We next tested if dystrophic microglia could …
Distribution Of Microglial Phenotypes As A Function Of Age And Alzheimer's Disease Neuropathology In The Brains Of People With Down Syndrome, Alessandra C. Martini, Alex M. Helman, Katie L. Mccarty, Ira T. Lott, Eric Doran, Frederick A. Schmitt, Elizabeth Head
Distribution Of Microglial Phenotypes As A Function Of Age And Alzheimer's Disease Neuropathology In The Brains Of People With Down Syndrome, Alessandra C. Martini, Alex M. Helman, Katie L. Mccarty, Ira T. Lott, Eric Doran, Frederick A. Schmitt, Elizabeth Head
Sanders-Brown Center on Aging Faculty Publications
Introduction: Microglial cells play an important role in the development of Alzheimer's disease (AD). People with Down syndrome (DS) inevitably develop AD neuropathology (DSAD) by 40 years of age. We characterized the distribution of different microglial phenotypes in the brains of people with DS and DSAD.
Methods: Autopsy tissue from the posterior cingulate cortex (PCC) from people with DS, DSAD, and neurotypical controls was immunostained with the microglial marker Iba1 to assess five microglia morphological types.
Results: Individuals with DS have more hypertrophic microglial cells in their white matter. In the gray matter, individuals with DSAD had significantly fewer ramified …
Tdp-43 Proteinopathy In Aging: Associations With Risk-Associated Gene Variants And With Brain Parenchymal Thyroid Hormone Levels, Peter T. Nelson, Zsombor Gal, Wang-Xia Wang, Dana M. Niedowicz, Sergey C. Artiushin, Samuel Wycoff, Angela Wei, Gregory A. Jicha, David W. Fardo
Tdp-43 Proteinopathy In Aging: Associations With Risk-Associated Gene Variants And With Brain Parenchymal Thyroid Hormone Levels, Peter T. Nelson, Zsombor Gal, Wang-Xia Wang, Dana M. Niedowicz, Sergey C. Artiushin, Samuel Wycoff, Angela Wei, Gregory A. Jicha, David W. Fardo
Pathology and Laboratory Medicine Faculty Publications
TDP-43 proteinopathy is very prevalent among the elderly (affecting at least 25% of individuals over 85 years of age) and is associated with substantial cognitive impairment. Risk factors implicated in age-related TDP-43 proteinopathy include commonly inherited gene variants, comorbid Alzheimer's disease pathology, and thyroid hormone dysfunction. To test parameters that are associated with aging-related TDP-43 pathology, we performed exploratory analyses of pathologic, genetic, and biochemical data derived from research volunteers in the University of Kentucky Alzheimer's Disease Center autopsy cohort (n = 136 subjects). Digital pathologic methods were used to discriminate and quantify both neuritic and intracytoplasmic TDP-43 pathology …
Neuropathological And Genetic Correlates Of Survival And Dementia Onset In Synucleinopathies: A Retrospective Analysis, David J. Irwin, Murray Grossman, Daniel Weintraub, Howard I. Hurtig, John E. Duda, Sharon X. Xie, Edward B. Lee, Vivianna M. Van Deerlin, Oscar L. Lopez, Julia K. Kofler, Peter T. Nelson, Gregory A. Jicha, Randy Woltjer, Joseph F. Quinn, Jeffery Kaye, James B. Leverenz, Debby Tsuang, Katelan Longfellow, Dora Yearout, Walter Kukull, C. Dirk Keene, Thomas J. Montine, Cyrus P. Zabetian, John Q. Trojanowski
Neuropathological And Genetic Correlates Of Survival And Dementia Onset In Synucleinopathies: A Retrospective Analysis, David J. Irwin, Murray Grossman, Daniel Weintraub, Howard I. Hurtig, John E. Duda, Sharon X. Xie, Edward B. Lee, Vivianna M. Van Deerlin, Oscar L. Lopez, Julia K. Kofler, Peter T. Nelson, Gregory A. Jicha, Randy Woltjer, Joseph F. Quinn, Jeffery Kaye, James B. Leverenz, Debby Tsuang, Katelan Longfellow, Dora Yearout, Walter Kukull, C. Dirk Keene, Thomas J. Montine, Cyrus P. Zabetian, John Q. Trojanowski
Sanders-Brown Center on Aging Faculty Publications
Background
Great heterogeneity exists in survival and the interval between onset of motor symptoms and dementia symptoms across synucleinopathies. We aimed to identify genetic and pathological markers that have the strongest association with these features of clinical heterogeneity in synucleinopathies.
Methods
In this retrospective study, we examined symptom onset, and genetic and neuropathological data from a cohort of patients with Lewy body disorders with autopsy-confirmed α synucleinopathy (as of Oct 1, 2015) who were previously included in other studies from five academic institutions in five cities in the USA. We used histopathology techniques and markers to assess the burden of …
Widespread Tau Seeding Activity At Early Braak Stages, Jennifer L. Furman, Jaime Vaquer-Alicea, Charles L. White, Nigel J. Cairns, Peter T. Nelson, Marc I. Diamond
Widespread Tau Seeding Activity At Early Braak Stages, Jennifer L. Furman, Jaime Vaquer-Alicea, Charles L. White, Nigel J. Cairns, Peter T. Nelson, Marc I. Diamond
Pathology and Laboratory Medicine Faculty Publications
Transcellular propagation of tau aggregates may underlie the progression of pathology in Alzheimer's disease (AD) and other tauopathies. Braak staging (B1, B2, B3) is based on phospho-tau accumulation within connected brain regions: entorhinal cortex (B1); hippocampus/limbic system (B2); and frontal and parietal lobes (B3). We previously developed a specific and sensitive assay that uses flow cytometry to quantify tissue seeding activity based on fluorescence resonance energy transfer (FRET) in cells that stably express tau reporter proteins. In a tauopathy mouse model, we have detected seeding activity far in advance of histopathological changes. It remains unknown whether individuals with AD also …
Abcc9 Gene Polymorphism Is Associated With Hippocampal Sclerosis Of Aging Pathology, Peter T. Nelson, Steven Estus, Erin L. Abner, Ishita Parikh, Manasi Malik, Janna H. Neltner, Eseosa Ighodaro, Wang-Xia Wang, Bernard R. Wilfred, Li-San Wang, Walter A. Kukull, Kannabiran Nandakumar, Mark L. Farman, Wayne W. Poon, Maria M. Corrada, Claudia H. Kawas, David H. Cribbs, David A. Bennett, Julie A. Schneider, Eric B. Larson, Paul K. Crane, Otto Valladares, Frederick A. Schmitt, Richard J. Kryscio, Gregory A. Jicha, Charles D. Smith, Stephen W. Scheff, Joshua A. Sonnen, Jonathan L. Haines, Margaret A. Pericak-Vance, Richard Mayeux, Lindsay A. Farrer, Linda J. Van Eldik, Craig Horbinski, Robert C. Green, Marla Gearing, Leonard W. Poon, Patricia L. Kramer, Randall L. Woltjer, Thomas J. Montine, Amanda B. Partch, Alexander J. Rajic, Katierose Richmire, Sarah E. Monsell, Gerard D. Schellenberg, David W. Fardo
Abcc9 Gene Polymorphism Is Associated With Hippocampal Sclerosis Of Aging Pathology, Peter T. Nelson, Steven Estus, Erin L. Abner, Ishita Parikh, Manasi Malik, Janna H. Neltner, Eseosa Ighodaro, Wang-Xia Wang, Bernard R. Wilfred, Li-San Wang, Walter A. Kukull, Kannabiran Nandakumar, Mark L. Farman, Wayne W. Poon, Maria M. Corrada, Claudia H. Kawas, David H. Cribbs, David A. Bennett, Julie A. Schneider, Eric B. Larson, Paul K. Crane, Otto Valladares, Frederick A. Schmitt, Richard J. Kryscio, Gregory A. Jicha, Charles D. Smith, Stephen W. Scheff, Joshua A. Sonnen, Jonathan L. Haines, Margaret A. Pericak-Vance, Richard Mayeux, Lindsay A. Farrer, Linda J. Van Eldik, Craig Horbinski, Robert C. Green, Marla Gearing, Leonard W. Poon, Patricia L. Kramer, Randall L. Woltjer, Thomas J. Montine, Amanda B. Partch, Alexander J. Rajic, Katierose Richmire, Sarah E. Monsell, Gerard D. Schellenberg, David W. Fardo
Pathology and Laboratory Medicine Faculty Publications
Hippocampal sclerosis of aging (HS-Aging) is a high-morbidity brain disease in the elderly but risk factors are largely unknown. We report the first genome-wide association study (GWAS) with HS-Aging pathology as an endophenotype. In collaboration with the Alzheimer's Disease Genetics Consortium, data were analyzed from large autopsy cohorts: (#1) National Alzheimer's Coordinating Center (NACC); (#2) Rush University Religious Orders Study and Memory and Aging Project; (#3) Group Health Research Institute Adult Changes in Thought study; (#4) University of California at Irvine 90+ Study; and (#5) University of Kentucky Alzheimer's Disease Center. Altogether, 363 HS-Aging cases and 2,303 controls, all pathologically …
Hippocampal Sclerosis Of Aging, A Prevalent And High-Morbidity Brain Disease, Peter T. Nelson, Charles D. Smith, Erin L. Abner, Bernard J. Wilfred, Wang-Xia Wang, Janna H. Neltner, Michael Baker, David W. Fardo, Richard J. Kryscio, Stephen W. Scheff, Gregory A. Jicha, Kurt A. Jellinger, Linda J. Van Eldik, Frederick A. Schmitt
Hippocampal Sclerosis Of Aging, A Prevalent And High-Morbidity Brain Disease, Peter T. Nelson, Charles D. Smith, Erin L. Abner, Bernard J. Wilfred, Wang-Xia Wang, Janna H. Neltner, Michael Baker, David W. Fardo, Richard J. Kryscio, Stephen W. Scheff, Gregory A. Jicha, Kurt A. Jellinger, Linda J. Van Eldik, Frederick A. Schmitt
Sanders-Brown Center on Aging Faculty Publications
Hippocampal sclerosis of aging (HS-Aging) is a causative factor in a large proportion of elderly dementia cases. The current definition of HS-Aging rests on pathologic criteria: neuronal loss and gliosis in the hippocampal formation that is out of proportion to AD-type pathology. HS-Aging is also strongly associated with TDP-43 pathology. HS-Aging pathology appears to be most prevalent in the oldest-old: autopsy series indicate that 5-30 % of nonagenarians have HS-Aging pathology. Among prior studies, differences in study design have contributed to the study-to-study variability in reported disease prevalence. The presence of HS-Aging pathology correlates with significant cognitive impairment which is …
Application Of Magnetic Resonance Imaging To Understanding The Pathogenesis Of The X-Linked Leukodystrophy Pelizaeus-Merzbacher Disease, Jeremy Jerome Laukka
Application Of Magnetic Resonance Imaging To Understanding The Pathogenesis Of The X-Linked Leukodystrophy Pelizaeus-Merzbacher Disease, Jeremy Jerome Laukka
Wayne State University Dissertations
Myelin is a multilamellar membrane structure surrounding axons in both the CNS and PNS that facilitates nerve conduction. In the CNS, myelin is synthesized by oligodendrocytes, while in the PNS, myelin is synthesized by Schwann cells. In the CNS, Proteolipid protein 1 (PLP1), an integral membrane protein, is the major protein component of myelin, constituting ~50% of myelin protein. Mutations of the PLP1 gene in man cause a spectrum of neurological disease, ranging from the severe Pelizaeus-Merzbacher disease (PMD), that typically begins during infancy with nystagmus, seizures and hypotonia and evolves into spastic quadriparesis, cognitive impairment and ataxia, to ¡¥pure¡¦ …